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Wearable magnetoencephalography based on optically pumped magnetometers (OPM-MEG) offers non-invasive and high-fidelity measurement of human brain electrophysiology. The flexibility of OPM-MEG also means it can be deployed in participants of all ages and permits scanning during movement. However, the magnetic fields generated by neuronal currents - which form the basis of the OPM-MEG signal - are much smaller than environmental fields, and this means measurements are highly sensitive to interference. Further, OPMs have a low dynamic range, and should be operated in near-zero background field. Scanners must therefore be housed in specialised magnetically shielded rooms (MSRs), formed from multiple layers of shielding material. The MSR is a critical component, and current OPM-optimised shields are large (>3 m in height), heavy (>10,000 kg) and expensive (with up to 5 layers of material). This restricts the uptake of OPM-MEG technology. Here, we show that the application of the Maxwell filtering techniques signal space separation (SSS) and its spatiotemporal extension (tSSS) to OPM-MEG data can isolate small signals of interest measured in the presence of large interference. We compare phantom recordings and MEG data from a participant performing a motor task in a state-of-the-art 5-layer MSR, to similar data collected in a lightly shielded room: application of tSSS to data recorded in the lightly shielded room allowed accurate localisation of a dipole source in the phantom and neuronal sources in the brain. Our results point to future deployment of OPM-MEG in lighter, cheaper and easier-to-site MSRs which could catalyse widespread adoption of the technology.

Neural oscillations mediate the coordination of activity within and between brain networks, supporting cognition and behaviour. How these processes develop throughout childhood is not only an important neuroscientific question but could also shed light on the mechanisms underlying neurological and psychiatric disorders. However, measuring the neurodevelopmental trajectory of oscillations has been hampered by confounds from instrumentation. In this paper, we investigate the suitability of a disruptive new imaging platform - optically pumped magnetometer-based magnetoencephalography (OPM-MEG) - to study oscillations during brain development. We show how a unique 192-channel OPM-MEG device, which is adaptable to head size and robust to participant movement, can be used to collect high-fidelity electrophysiological data in individuals aged between 2 and 34 years. Data were collected during a somatosensory task, and we measured both stimulus-induced modulation of beta oscillations in sensory cortex, and whole-brain connectivity, showing that both modulate significantly with age. Moreover, we show that pan-spectral bursts of electrophysiological activity drive task-induced beta modulation, and that their probability of occurrence and spectral content change with age. Our results offer new insights into the developmental trajectory of beta oscillations and provide clear evidence that OPM-MEG is an ideal platform for studying electrophysiology in neurodevelopment., Competing Interests: LR is a scientific advisor for Cerca Magnetics Limited, a company that sells equipment related to brain scanning using OPM-MEG, NR, DP, GR, MT No competing interests declared, EB is a director of Cerca Magnetics Limited, a company that sells equipment related to brain scanning using OPM-MEG. She also holds founding equity in Cerca Magnetics Limited, NH, RH, RB is a scientific advisor for Cerca Magnetics Limited, a company that sells equipment related to brain scanning using OPM-MEG. He also holds founding equity in Cerca Magnetics Limited, VS is the founding director of QuSpin, a company that builds and sells OPM sensors, CD, JO works for QuSpin, a company that builds and sells OPM sensors, MB is a director of Cerca Magnetics Limited, a company that sells equipment related to brain scanning using OPM-MEG. He also holds founding equity in Cerca Magnetics Limited, (© 2024, Rier, Rhodes et al.)

The ability to collect high-quality neuroimaging data during ambulatory participant movement would enable a wealth of neuroscientific paradigms. Wearable magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs) has the potential to allow participant movement during a scan. However, the strict zero magnetic field requirement of OPMs means that systems must be operated inside a magnetically shielded room (MSR) and also require active shielding using electromagnetic coils to cancel residual fields and field changes (due to external sources and sensor movements) that would otherwise prevent accurate neuronal source reconstructions. Existing active shielding systems only compensate fields over small, fixed regions and do not allow ambulatory movement. Here we describe the matrix coil, a new type of active shielding system for OPM-MEG which is formed from 48 square unit coils arranged on two planes which can compensate magnetic fields in regions that can be flexibly placed between the planes. Through the integration of optical tracking with OPM data acquisition, field changes induced by participant movement are cancelled with low latency (25 ms). High-quality MEG source data were collected despite the presence of large (65 cm translations and 270° rotations) ambulatory participant movements., Competing Interests: Declaration of Competing Interest E.B. and M.J.B. are directors of Cerca Magnetics Limited, a spin-out company whose aim is to commercialise aspects of OPM-MEG technology. E.B., M.J.B., R.B., N.H. and R.H. hold founding equity in Cerca Magnetics Limited and R.B., N.H. and R.H. sit on the scientific advisory board. M.R. is an employee of Cerca Magnetics Limited. V.S. is the founding director of QuSpin Inc., a commercial entity selling the OPM magnetometers used in this work. J.O. is an employee of QuSpin Inc. N.H, M.J.B., and R.B. declare that they have a patent pending to the UK Government Intellectual Property Office (Application No. GB2109459.4) regarding the multi-coil active magnetic shielding systems described in this work. P.J.H, T.M.F, M.J.B., and R.B. declare that they have a worldwide patent (WIPO Patent Application WO/2021/053356) regarding related electromagnetic coil design techniques. The remaining authors, J.L., L.J.E., T.M.T. L.R., G.R.R. and P.G. declare no competing interests, (Copyright © 2023. Published by Elsevier Inc.)

Optically pumped magnetometers (OPMs) are an emerging lightweight and compact sensor that can measure magnetic fields generated by the human brain. OPMs enable construction of wearable magnetoencephalography (MEG) systems, which offer advantages over conventional instrumentation. However, when trying to measure signals at low frequency, higher levels of inherent sensor noise, magnetic interference and movement artefact introduce a significant challenge. Accurate characterisation of low frequency brain signals is important for neuroscientific, clinical, and paediatric MEG applications and consequently, demonstrating the viability of OPMs in this area is critical. Here, we undertake measurement of theta band (4-8 Hz) neural oscillations and contrast a newly developed 174 channel triaxial wearable OPM-MEG system with conventional (cryogenic-MEG) instrumentation. Our results show that visual steady state responses at 4 Hz, 6 Hz and 8 Hz can be recorded using OPM-MEG with a signal-to-noise ratio (SNR) that is not significantly different to conventional MEG. Moreover, we measure frontal midline theta oscillations during a 2-back working memory task, again demonstrating comparable SNR for both systems. We show that individual differences in both the amplitude and spatial signature of induced frontal-midline theta responses are maintained across systems. Finally, we show that our OPM-MEG results could not have been achieved without a triaxial sensor array, or the use of postprocessing techniques. Our results demonstrate the viability of OPMs for characterising theta oscillations and add weight to the argument that OPMs can replace cryogenic sensors as the fundamental building block of MEG systems., Competing Interests: Conflicts of interest V.S. is the founding director of QuSpin, a commercial entity selling OPM magnetometers. J.O. and C.D. are employees of QuSpin. E.B. and M.J.B. are directors of Cerca Magnetics Limited, a spin-out company whose aim is to commercialise aspects of OPM-MEG technology. E.B., M.J.B., R.B., N.H. and R.H. hold founding equity in Cerca Magnetics Limited., (Copyright © 2023. Published by Elsevier Inc.)

Epilepsy is a highly heterogeneous neurological disorder with variable etiology, manifestation, and response to treatment. It is imperative that new models of epileptiform brain activity account for this variability, to identify individual needs and allow clinicians to curate personalized care. Here, we use a hidden Markov model (HMM) to create a unique statistical model of interictal brain activity for 10 pediatric patients. We use magnetoencephalography (MEG) data acquired as part of standard clinical care for patients at the Children's Hospital of Philadelphia. These data are routinely analyzed using excess kurtosis mapping (EKM); however, as cases become more complex (extreme multifocal and/or polymorphic activity), they become harder to interpret with EKM. We assessed the performance of the HMM against EKM for three patient groups, with increasingly complicated presentation. The difference in localization of epileptogenic foci for the two methods was 7 ± 2 mm (mean ± SD over all 10 patients); and 94% ± 13% of EKM temporal markers were matched by an HMM state visit. The HMM localizes epileptogenic areas (in agreement with EKM) and provides additional information about the relationship between those areas. A key advantage over current methods is that the HMM is a data-driven model, so the output is tuned to each individual. Finally, the model output is intuitive, allowing a user (clinician) to review the result and manually select the HMM epileptiform state, offering multiple advantages over previous methods and allowing for broader implementation of MEG epileptiform analysis in surgical decision-making for patients with intractable epilepsy., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Magnetoencephalography (MEG) measures the small magnetic fields generated by current flow in neural networks, providing a noninvasive metric of brain function. MEG is well established as a powerful neuroscientific and clinical tool. However, current instrumentation is hampered by cumbersome cryogenic field-sensing technologies. In contrast, MEG using optically pumped magnetometers (OPM-MEG) employs small, lightweight, noncryogenic sensors that provide data with higher sensitivity and spatial resolution, a natural scanning environment (including participant movement), and adaptability to any age. However, OPM-MEG is new and the optimum way to design a system is unknown. Here, we construct a novel, 90-channel triaxial OPM-MEG system and use it to map motor function during a naturalistic handwriting task. Results show that high-precision magnetic field control reduced background fields to ∼200 pT, enabling free participant movement. Our triaxial array offered twice the total measured signal and better interference rejection compared to a conventional (single-axis) design. We mapped neural oscillatory activity to the sensorimotor network, demonstrating significant differences in motor network activity and connectivity for left-handed versus right-handed handwriting. Repeatability across scans showed that we can map electrophysiological activity with an accuracy ∼4 mm. Overall, our study introduces a novel triaxial OPM-MEG design and confirms its potential for high-performance functional neuroimaging., (© 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

Mild traumatic brain injury (mTBI) poses a considerable burden on healthcare systems. Whilst most patients recover quickly, a significant number suffer from sequelae that are not accompanied by measurable structural damage. Understanding the neural underpinnings of these debilitating effects and developing a means to detect injury, would address an important unmet clinical need. It could inform interventions and help predict prognosis. Magnetoencephalography (MEG) affords excellent sensitivity in probing neural function and presents significant promise for assessing mTBI, with abnormal neural oscillations being a potential specific biomarker. However, growing evidence suggests that neural dynamics are (at least in part) driven by transient, pan-spectral bursting and in this paper, we employ this model to investigate mTBI. We applied a Hidden Markov Model to MEG data recorded during resting state and a motor task and show that previous findings of diminished intrinsic beta amplitude in individuals with mTBI are largely due to the reduced beta band spectral content of bursts, and that diminished beta connectivity results from a loss in the temporal coincidence of burst states. In a motor task, mTBI results in diminished burst amplitude, altered modulation of burst probability during movement, and a loss in connectivity in motor networks. These results suggest that, mechanistically, mTBI disrupts the structural framework underlying neural synchrony, which impairs network function. Whilst the damage may be too subtle for structural imaging to see, the functional consequences are detectable and persist after injury. Our work shows that mTBI impairs the dynamic coordination of neural network activity and proposes a potent new method for understanding mTBI., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The global incidence of traumatic brain injuries is rising, with at least 80% being classified as mild. These mild injuries are not visible on routine clinical imaging. The potential clinical role of a specific imaging biomarker be it diagnostic, prognostic or directing and monitoring progress of personalised treatment and rehabilitation has driven the exploration of several new neuroimaging modalities. This systematic review examined the evidence for magnetoencephalography (MEG) to provide an imaging biomarker in mild traumatic brain injury (mTBI)., Methods: Our review was prospectively registered on PROSPERO: CRD42019151387. We searched EMBASE, MEDLINE, trial registers, PsycINFO, Cochrane Library and conference abstracts and identified 37 papers describing MEG changes in mTBI eligible for inclusion. Since meta-analysis was not possible, based on the heterogeneity of reported outcomes, we provide a narrative synthesis of results., Results: The two most promising MEG biomarkers are excess resting state low frequency power, and widespread connectivity changes in all frequency bands. These may represent biomarkers with potential for diagnostic application, which reflect time sensitive changes, or may be capable of offering clinically relevant prognostic information. In addition, the rich data that MEG produces are well-suited to new methods of machine learning analysis, which is now being actively explored., Interpretation: MEG reveals several promising biomarkers, in the absence of structural abnormalities demonstrable with either computerised tomography or magnetic resonance imaging. This review has not identified sufficient evidence to support routine clinical use of MEG in mTBI currently. However, verifying MEG's potential would help meet an urgent clinical need within civilian, sports and military medicine., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)